We propose to form the Northeastern Ohio Animal Imaging Resource Center (NOAIRC) to provide the many regional cancer researchers with state-of-the-art small animal, molecular and cellular imaging facilities and expertise. Systems will include a combined micro- x-ray computed tomography/SPECT system, a clinical SPECT system with pin-hole collimators, a high resolution micro-PET system, and 7T and g.4T small animal MR imaging and spectroscopy systems. All are already on-site or ordered from recent grant awards and institutional sources. With an SAIRP award, we will acquire a biotumines- cence/fluorescence imaging system to facilitate reporter gene methods and new opportunities in novel agents (e.g., quan- tum dots). We will also create small animal optical coherence tomography with color Doppler and microscopic OCT to promote in vivo spectroscopic methods and high spatial and temporal analysis of structure and function (e.g., perfusion). Interdisciplinary backing for this project is unprecedented with financial and other commitments from three schools of Case Western Reserve University (Medicine, Engineering, Arts & Sciences), the University Hospitals of Cleveland, the Case Comprehensive Cancer Center, and the State of Ohio. In addition to core resources via nuclear imaging, MR imag- ing and spectroscopy, bioluminescence/fluorescence, and OCT, the NOAIRC will also provide an integrated environment with core facilities in quantitative image analysis and visualization, animal welfare/experiment preparation and novel imag- ing agents like functionalized liposomes or CEST agents. This latter core integrates with our radionuclide imaging capabili- ties, our ongoing biomolecular and nanoscale engineering for targeted therapeutics initiative, ongoing research in reporter genes, and a P20 In-vivo and molecular Imaging Center planning grant to add strategic strength in molecular imaging. All of these will be within a single facility to promote cross-collaboration and interdisciplinary research, This proposal brings together researchers in imaging with the many regional scientists who are studying cancer biology via small animal models and rapidly gaining an appreciation of the power of in vivo imaging. We aim to advance small animal imaging technology by developing new image acquisition and analysis methods, new methods in reporter genes and functionalized agents, and pharmacokinetic modeling. We will apply developments to experiments in cancer biology and therapy. Animal welfare/preparation research will focus on analysis of physiologic effects of anesthesia and develop- ing new formulations that maintain the physiology to be measured, while providing state-of-the-art methods for blood sam- pling and monitoring. The NOAIRC will include a strong educational focus to create a long-range impact. It will invigorate strong Ph.D. programs in imaging already at Case. It will strengthen educational programs for basic and clinical scientists in cancer via integration with existing T32 and K12 grants and promote new horizons via K25 proposals. The result will be clinicians, scientists, and engineers trained for the next generation of conventional and molecular imaging techniques. PERFORMANCESITE(S) (organization,city,state) 1. University Hospitals of Cleveland, Department of Radiology, 11100 Euclid Ave. Cleveland, OH 44106 2. Case Western Reserve University (CWRU) School of Medicine 3. CWRU Department of Biomedical Engineering, Wickenden Bldg, 10900 Euclid Ave., Cleveland, OH 44106 4. CWRU Comprehensive Cancer Center, Wearn Bldg., 11100 Euclid Avenue, Cleveland, OH 44106 5. University Hospitals of Cleveland, Department of Surgery, 533 Wearn Building 6. University Hospitals of Cleveland, Department of Medicine, Division of Gastroenterology, 248 Wearn Building KEYPERSONNEL.Seeinstructions. Usecontinuationpagesas neededto providethe requiredinformationin theformatshownbelow. Startwith PrincipalInvestigator.List allotherkey personnelinalphabeticalorder,last namefirst. Name Organization Rolecn Project TECHNICAL Jeffrey L. Duerk, Ph.D. CWRU and Univ. Hosp. Cleveland (UHC), PI Radiology, BME David A. Wilson, Ph.D. CWRU- BME Co-investigator Andrew Rollins, Ph.D. CWRU BME Co-investigator Ray Muzio, Ph.D. CWRU - Radiology, BME Co-investigator Zhenghong Lee, Ph.D. CWRU- Radiology, BME Co-investigator, Base Grant Recipient Jinming Gao, Ph.D. CWRU- BME Co-investigator, Base Grant Recipient Mark "Marty" Pagel, Ph.D. CWRU- BME Co-investigator Disclosure Permission Statement. Applicable to SBIR/STTR Only. See instructions. [] Yes [] No []PHS 398(Rev.05/0_) Page2 FormPage2 Use_/2-incMh ARGINS.Numberpagesconsecutivelyat the bottomthroughouttheapplication.Dono_u_sttesuffixessuchas 3a,3b. PrincipIanlvesti.qator/ProD.iqreracmto(Lrast, first, middle): Duerk, KEY PERSONNEL. (Continued) Name Organization Maryanne Fitzmaurice, MD, PhD. CWRU and Univ. Hosp. Cleveland (UHC), Pathology Clemens Burda, Ph.D. CWRU Chemistry Peter Faulhaber, MD Department of Radiology, University Hospi- tals of Cleveland and CWRU Marc Berridge, Ph.D. CWRU Chemistry Claudia Hillenbrand, Ph.D. CWRU and Univ. Hosp. Cleveland (UHC), Radiology, BME Nan Kleinman, DVM CWRU-Animal Res. Center Chris Flask, Ph.D. CWRU Radiology, Cancer Center Jeffrey L. Role on Project Investigator Investigator Investigator Investigator, Radiochemist Investigator Co-investigator Co-investigator Stan Gerson, MD Ruth Keri, Ph.D. Sandy Markowitz, MD, Ph.D. Joe Nadeau, Ph.D. Nancy Oleinick, Ph.D. Scot Remick, MD Bing-Cheng Wang GQ Zhang Gheorghe Mateescu CANCER BIOLOGY- Base Grants CWRU Hematology/Oncology CWRU Pharmacology CWRU Cancer Genetics and Howard Hughes Medical Institute CWRU Genetics CWRU Oncology, UHC Radiation Oncology CWRU Hematology/Oncology CWRU Medicine, Nephrology VISITING PROFESSORS CWRU Electrical Engineering and Com- puter Science CWRU Chemistry SUPPORT STAFF John Jesberger, BS CWRU and UHC Radiology Greg Wojtkiewicz CWRU and UHC Radiology Base Grant Recipient Base Grant Recipient Base Grant Recipient Base Grant Recipient Base Grant Recipient Base Grant Recipient Investigator Visiting Professor Visiting Professor Research Associate Research Associate PHS 398 (Rev. 05/01) Page FormPage3 Use 1/2-inchMARGINS. Numberpagesconsecutivelyat the bottom throughoutthe application.Do no_u.jtsesuffixessuch as 3a, 3b. Principal Investi.qator/Pro.qram Director (Last, first, middle): Duerk, Jeffrey L. RESEARCH GRANT TABLE OF CONTENTS Face Page ............................................................................................................................. Description,